Exploring bacterial lectin recognition events of synthetic mucin glycopeptide ligands

Session: 
S10.2 Cell surface glycans
Code: 
OL10.2.4
Location (hall): 
Mannose
Start/end time: 
Thursday, July 4, 2019 - 18:00 to 18:15
Ulrika
Westerlind

Ulrika Westerlind1

1Umeå University, Umeå, Sweden

Mucins are densely glycosylated proteins that populate the cell-surface of epithelial tissues.[1] The extracellular tandem repeat peptide regions rich on proline, threonine and serine residues characterize the mucins. By display of O-glycans often organized in a multivalent fashion, the mucins and mucin like glycoproteins are involved in a plethora of cell-surface binding events.[2] Glycans on mucins often act as ligands for invading pathogens, studies of such interactions are useful for characterization of microbes and viruses as well as to develop new anti-adhesive drugs. By chemical synthesis of well-defined glycan and glycopeptide probes we aim to identify and map the functions of mucins and their interacting binding partners involved in infection processes.

In recent years we have developed efficient total synthesis strategies to construct over 300 different mucin O-glycopeptides modified with short tumor-associated glycan structures and more complex elongated mucin core structures.[3-6] Using enzymes, the elongated core structures were further diversified by fucosylation, sialylation and polyLacNAc. The synthetic glycopeptides have been immobilized on biocompatible hydrogel slides that display the glycopeptides in a multivalent mode. Our recent microarray analysis results evaluating  bacterial lectin recognition of mucin glycopeptide epitopes will be presented at Eurocarb.

References: 
  1. Rose, M. C.; Voynow, J. A., Phys. Rev. 2006, 86, 245-278.
  2. Carlstedt, I.; Davies, J. R., Biochem. Soc. Trans. 1997, 25, 214-219.
  3. Pett, C.; Schorlemer, M.; Westerlind, U., Chem. Eur. J. 2013, 19, 17001-17010.
  4. Pett, C.; Westerlind, U., Chem. Eur. J. 2014, 20, 7287-7299.
  5. Pett, C.; Cai, H.; Liu, J.; Palitzsch, B.; Schorlemer, M.; Hartmann, S.; Stergiou, N.; Lu, M.; Kunz, H.; Schmitt, E.; Westerlind, U,.Chem. Eur. J. 2017, 23, 3875-3884.
  6. Pett, C.; Nasir, W.; Sihlbom, C.; Olsson, B. M.; Caixeta, V.; Schorlemer, M.; Zahedi, R. P.; Larsson, G.; Nilsson, J.; Westerlind, U. Angew. Chem. Int. Ed. 2018 57, 9320-9324.

Sponsors

Sponsors